The proposed research will involve investigation of the action of certain cardiovascular drugs which inhibit or augment the effects of the sympathetic nervous system on cardiovascular function. Under consideration will be the treatment of congestive heart failure, hypertension, and angina pectoris. Studies will be performed in normal human subjects, in patients with cardiovascular disease, and in experimental animals. Vasodilators have recently been found to be useful in the therapy of essential hypertension. These have been used extensively in conjunction with beta adrenergic antagonists and diuretics. We are interested in evaluating the interaction of vasodilators, beta adrenergic antagonists and diuretics and investigating the basic mechanism of action of each drug individually. Studies are being conducted in the area of pharmacokinetic evaluation of propranolol, in the area of renin secretion, and in the area of general pharmacologic activity of minoxidil. Studies will also be carried out to evaluate clinical pharmacologic problems relating to the cardiac glycosides. Pharmacokinetic principles will be developed for assessing the function of disposition of digoxin in patients with chronic congestive heart failure. The therapeutic activity and the pharmacokinetic fate of theophylline will be evaluated in patients with chronic pulmonary disease. A new method is in the process of being developed to quantify theophylline and its metabolites both in blood and in urine. This method will be applied to therapeutic assessment of the effects of theophylline in patients with pulmonary disease.